This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Kinases are important targets for structure-based drug discovery. The central challenge in designing kinase inhibitors is that many inhibitors bind to the highly conserved ATP-binding site. In an effort to identify specificity modes, we are comparing and contrasting the x-ray crystal structures of inhibitors bound to the kinase proteins in our project portfolio. We have already solved inhibitor-bound structures for AIK, Syk, IGF1r, FAK, DPP-IV, all of which are therapeutic targets. This proposal focuses primarily on design of AIK inhibitors.